The European Commission ( EC ) has approved Sarclisa ( Isatuximab ) in combination with Carfilzomib and Dexamethasone ( Kd ) for the treatment of adult patients with relapsed multiple myeloma who have received at least one prior therapy.
This marks the second EC approval of Sarclisa in combination with a standard of care regimen in less than 12 months.
This EC approval closely follows the U.S. Food and Drug Administration ( FDA ) approval of Sarclisa for a similar indication in March 2021.
In June 2020, Sarclisa received EC approval in combination with another standard of care regimen, Pomalidomide and Dexamethasone ( Pom-Dex ), for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior therapies including Lenalidomide and a proteasome inhibitor and have demonstrated disease progression on the last therapy.
The new approval is based on data from the phase 3 IKEMA study, a randomized, multi-center, open label clinical trial that enrolled 302 patients with relapsed multiple myeloma across 69 centers spanning 16 countries.
The primary endpoint of IKEMA was progression free survival ( PFS ). While median PFS, defined as time to disease progression or death, for Kd was 19.15 months, the median PFS for patients receiving Sarclisa added to Carfilzomib and Dexamethasone ( Sarclisa combination therapy; n=179 ) had not been reached at the time of the pre-planned interim analysis.
Sarclisa combination therapy reduced the risk of disease progression or death by 47% ( hazard ratio, HR=0.531, 99% CI 0.318-0.889, p=0.0007 ) versus standard of care Kd alone in patients with multiple myeloma.
Secondary endpoints of the IKEMA trial assessed the depth of response for Sarclisa combination therapy compared to Kd, including overall response rate ( ORR ), complete response ( CR ), very good partial response ( VGPR ) and minimal residual disease ( MRD )-negative response.
The overall response rate remained similar for each arm at 86.6% for the Sarclisa combination therapy versus 82.9% for Kd but was not statistically significant.
The rate of complete response was 39.7% in the Sarclisa combination therapy arm and 27.6% in the Kd arm.
The rate of very good partial response or better was 72.6% for patients receiving Sarclisa combination therapy and 56.1% for patients receiving Kd.
MRD-negativity was observed in 29.6% of patients in the Sarclisa combination therapy arm versus 13% of patients in the Kd arm, indicating that nearly 30% of patients treated with Sarclisa combination therapy has achieved undetectable levels of multiple myeloma at 10-5 sensitivity as measured by next generation sequencing ( NGS ).
At the time of the interim analysis, overall survival ( OS ) data were still immature.
The most frequent adverse reactions ( 20% or more ) were infusion reactions ( 45.8% ), hypertension ( 36.7% ), diarrhea ( 36.2% ), upper respiratory tract infection ( 36.2% ), pneumonia ( 28.8% ), fatigue ( 28.2% ), dyspnea ( 27.7% ), insomnia ( 23.7% ), bronchitis ( 22.6% ), and back pain ( 22.0% ).
Serious adverse reactions occurred in 59.3% of patients receiving Sarclisa combination therapy and in 57.4% of patients receiving Kd.
The most frequent serious adverse reaction was pneumonia ( 21.5% ).
Permanent discontinuation of treatment because of adverse reactions was reported in 8.5% of patients treated with Sarclisa combination therapy and in 13.9% of patients treated with Kd.
Fatal adverse events were reported in 3.4% of patients treated with Sarclisa combination therapy and in 3.3% of patients treated with Kd.
Sarclisa is a monoclonal antibody that binds to a specific epitope on the CD38 receptor on multiple myeloma cells. It is designed to work through multiple mechanisms of action including programmed tumor cell death ( apoptosis ) and immunomodulatory activity.
CD38 is highly and uniformly expressed on the surface of multiple myeloma cells, making it a potential target for antibody-based therapeutics such as Sarclisa.
Multiple myeloma is the second most common hematologic malignancy, with more than 130,000 new diagnoses worldwide yearly.
In Europe, approximately 39,000 patients are diagnosed with multiple myeloma each year.
Despite available treatments, multiple myeloma remains an incurable malignancy, and is associated with significant patient burden. Since multiple myeloma does not have a cure, most patients will relapse. ( Xagena )
Source: Sanofi, 2021